Table 2.
Simulation results for scenarios with surrogacy concordance (ΔS = ΔT = Δ). Mean(SS) is the mean sample size across hypothetical trials (to be compared with n = 2000). P(1), P(2), P(3), and P(Full) are the proportions of trials at interim checkpoints 1, 2, 3, or full follow-up, respectively, that switched endpoints and/or stopped early due to efficacy, inferiority, or futility, presented by endpoint used. The final column reports total percentages of observed discordance (switching) and each stopping reason across time points, by endpoint. Switching results are italicized for clarity, as they do not affect early stopping or average sample size.
| Δ | Mean(SS) | Reason | Endpoint | P(1) | P(2) | P(3) | P(Full) | Total |
|---|---|---|---|---|---|---|---|---|
| 0.8 | 975 | Switch S to T | - | - | - | - | 0.00 | |
| Efficacy | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| Inferiority | S | 1.00 | - | - | - | 1.00 | ||
| T | - | - | - | - | - | |||
| Futility | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| 2000 | Efficacy (O-F) | S | - | - | - | - | 0.00 | |
|
| ||||||||
| 0.9 | 999 | Switch S to T | - | - | - | - | 0.00 | |
| Efficacy | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| Inferiority | S | 0.61 | - | - | - | 0.61 | ||
| T | - | - | - | - | - | |||
| Futility | S | 0.39 | - | - | - | 0.39 | ||
| T | - | - | - | - | - | |||
| 2000 | Efficacy (O-F) | S | - | - | - | - | 0.00 | |
|
| ||||||||
| 1.0 | 1259 | Switch S to T | 0.02 | - | - | - | 0.02 | |
| Efficacy | S | - | 0.01 | - | - | 0.01 | ||
| T | 0.01 | - | - | - | 0.01 | |||
| Inferiority | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| Futility | S | 0.61 | 0.28 | 0.07 | 0.01 | 0.97 | ||
| T | 0.01 | - | - | - | 0.01 | |||
| 2000 | Efficacy (O-F) | S | - | - | - | 0.02 | 0.02 | |
|
| ||||||||
| 1.1 | 1380 | Switch S to T | - | - | - | - | 0.00 | |
| Efficacy | S | 0.48 | 0.33 | 0.11 | 0.05 | 0.97 | ||
| T | - | - | - | - | - | |||
| Inferiority | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| Futility | S | 0.02 | - | - | 0.01 | 0.03 | ||
| T | - | - | - | - | - | |||
| 1759 | Efficacy (O-F) | S | - | 0.55 | 0.36 | 0.09 | 1.00 | |
|
| ||||||||
| 1.2 | 1073 | Switch S to T | 0.01 | - | - | - | 0.01 | |
| Efficacy | S | 0.99 | - | - | - | 0.99 | ||
| T | 0.01 | - | - | - | 0.01 | |||
| Inferiority | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| Futility | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| 1316 | Efficacy (O-F) | S | 0.52 | 0.48 | - | - | 1.00 | |
|
| ||||||||
| 1.4 | 1110 | Switch S to T | - | - | - | - | 0.00 | |
| Efficacy | S | 1.00 | - | - | - | 1.00 | ||
| T | - | - | - | - | - | |||
| Inferiority | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| Futility | S | - | - | - | - | - | ||
| T | - | - | - | - | - | |||
| 1110 | Efficacy (O-F) | S | 1.00 | - | - | - | 1.00 | |